Amoksiklav Quiktab - instructions for use, dose, side effects, contraindications

Name of substance	Tablets 125 mg + 31.25 mg	Tablets 250 mg + 62.50 mg
Active substance:
Amoxicillin trihydrate	143.5 mg	287.0 mg
(corresponds to amoxicillin)	(125.0 mg)	(250.0 mg)
Potassium clavulanate (corresponding to	37.2 mg	74.4 mg
acid clavulanic acid)	(31.3 mg)	(62.5 mg)
Excipients:
Crospovidone	9.8 mg	19.7 mg
Silicon dioxide	2.5 mg	4.9 mg
Aromatizer sweet orange	9.8 mg	19.7 mg
Cellulose microcrystalline silicon-containing *	24.6 mg	49.2 mg
Sucralose	1.4 mg	2.7 mg
Sodium fumarate	7.1 mg	14.3 mg
Iron (III) oxide yellow, E 172	0.3 mg	0.6 mg
Mannitol	83.7 mg	167.4 mg

* contains 98% of microcrystalline cellulose and 2% of silicon dioxide colloid.

Description:

Round tablets from light yellow to yellow with impregnations of brown color and hemispherical deepening on both sides and with engraving "SN 57 "(dosage of 125 mg + 31.25 mg) or"SN 34 "(dosage of 250 mg + 62.25 mg) on the one hand.

Pharmacotherapeutic group:Antibiotic-penicillin semisynthetic + beta-lactamase inhibitor

ATX: & nbsp

J.01.C.R.02 Amoxicillin in combination with enzyme inhibitors

Pharmacodynamics:

Mechanism of action

Amoxicillin - a semisynthetic broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative microorganisms. In the same time, amoxicillin is subject to destruction by beta-lactamases, therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.

Clavulanic acid - Beta-lactamase inhibitor, structurally related to penicillins, has the ability to inactivate a wide spectrum of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often determine the resistance of bacteria, and is not effective against type I chromosomal beta-lactamases that are not inhibited by clavulanic acid.

The presence of clavulanic acid in the preparation protects amoxicillin from destruction by enzymes - beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin.

Below is the activity of a combination of amoxicillin with clavulanic acid in vitro:

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes, Streptococcus agalactiae^1,2, other beta-hemolytic stethococci^1,2, Staphylococcus aureus (sensitive to methicillin)¹, Staphylococcus saprophyticus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae Helicobacter pylori, Moraxella catarrhalis¹, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Gram-positive anaerobes: species of genus Clostridium, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, species of the genus Peptostreptococcus.

Gram-negative anaerobes: Bacteroides fragilis, species of the genus Bacteroides, species of the genus Capnocytophaga, Eikenella corrodens, Fusobacterium nucleatum, species of the genus Fusobacterium, species of the genus Porphyromonas, species of the genus Prevotella.

Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Bacteria for which the acquired resistance to a combination of amoxicillin and clavulanic acid is probable

Gram-negative aerobes: Escherichia coli¹, Klebsiella oxytoca, Klebsiella pneumoniae, species of the genus Klebsiella, Proteus mirabilis, Proteus vulgaris, species of the genus Proteus, species of the genus Salmonella, species of the genus Shigella.

Gram-positive aerobes: species of genus Corynebacterium, Enterococcus faecium, Streptococcus pneumoniae^1,2, group streptococci Viridans.

Bacteria that are naturally resistant to combination amoxicillin with clavulanic acid

Gram-negative aerobes: species of genus Acinetobacter, Citrobacter freundii, species of the genus Enterobacter, Hafnia alvei, Legionella pneumophila, Morganella morganii, species of the genus Providencia, species of the genus Pseudomonas, species of the genus Serratia, Stenotrophomonas maltophilia, Yersinia enterocolitica.

Other: Chlamydia pneumoniae, Chlamydia psittaci, species of the genus Chlamydia, Coxiella burnetii, species of the genus Mycoplasma.

¹for these bacteria, the clinical efficacy of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

²strains of these bacteria do not produce beta-lactamases.Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity to the combination of amoxicillin and clavulanic acid.

Pharmacokinetics:

Suction

The active substances of the preparation are quickly and completely absorbed from the gastrointestinal tract (GIT) after ingestion. Absorption of active substances is optimal in case of application of the preparation together with food.

The following are pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in studies when healthy volunteers aged 2-12 years received an amoxicillin / clavulanic acid (powder for oral suspension, 125 mg / 31.25 mg) in a dose 40 mg + 10 mg / kg per day.

The mean (± SD) pharmacokinetic parameters
Active matter	Dose (mg / kg)	FROM_m_Oh (mg / ml)	T_m_Oh (h)	AUC _(0-24_h) *(mg h / l)**	T_1/2 (h)
Amoxicillin, 125 mg	40	7,3±1,7	2,1 (1,2-3,0)	18,6±2,6	1,0±0,33
Clavulanic acid, 31.25 mg	10	2,7±1,6	1,6 (1,0-2,0)	5,5±3,1	0,94±0,05

FROM_max - maximum concentration in blood plasma;

T_max - time to reach the maximum concentration in the blood plasma;

AUC is the area under the concentration-time curve;

T_1/2- half-life.

Distribution

As with intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (in the gall bladder, abdominal organs, skin, fat and muscle tissues, synovial and peritoneal fluids, bile secretion) .

Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma bind to plasma proteins.

The distribution volume is about 0.3-0.4 l / kg for amoxicillin and about 0.2 l / kg for clavulanic acid.

Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier in non-inflamed meninges. Amoxicillin (like most penicillins) is excreted in breast milk. Traces of clavulanic acid can also be detected in breast milk.

With the exception of the possibility of developing sensitization, diarrhea and candidiasis of the oral mucosa,There are no other negative effects of amoxicillin and clavulanic acid on the health of infants on breastfeeding.

Studies of reproductive function in animals have shown that amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no adverse effect on the fetus.

Metabolism

About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys, through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.

Excretion

Amoxicillin is excreted primarily by the kidneys, whereas clavulanic acid is through both renal and extrarenal mechanisms. After a single dose of amoxicillin / clavulanic acid 250 mg / 125 mg approximately 60-70% amoxicillin and 40-65% clavulanic acid within the first 6 hours is excreted unchanged by the kidneys.

The mean half-life (T_1/2) amoxicillin / clavulanic acid is approximately 1 hour, the average total clearance is approximately 25 l / h in healthy patients. In various studies, it was found that the excretion of amoxicillin by the kidneys within 24 hours is approximately 50-85%, clavulanic acid 27-60%. The greatest amount of clavulanic acid is excreted within the first 2 hours after administration.

The pharmacokinetics of amoxicillin / clavulanic acid does not depend on the patient's sex.

Patients with impaired renal function

The total clearance of amoxicillin / clavulanic acid decreases in proportion to the decrease in renal function. The decrease in clearance is more pronounced for amoxicillin than for clavulanic acid, because most of the amoxicillin is excreted by the kidneys. Doses of the drug for renal failure should be selected taking into account the undesirability of cumulation of amoxicillin against the background of maintaining a normal level of clavulanic acid.

Both components of the drug are excreted during hemodialysis and insignificant amounts - with peritoneal dialysis.

Patients with impaired hepatic function

In patients with impaired liver function, the drug is used with caution, it is necessary to carry out constant monitoring of liver function.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to amoxicillin / clavulanic acid:

- infections of the upper respiratory tract and ENT organs (including acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);

- infection of the lower respiratory tract (acute bronchitis with bacterial superinfection, exacerbation of chronic bronchitis, pneumonia);

- urinary tract infections (eg, cystitis, urethritis, pyelonephritis);

- infection in gynecology and obstetrics;

- skin and soft tissue infections, including human and animal bites;

- infections of bone and connective tissues (eg, osteomyelitis);

- infection of the biliary tract (cholecystitis, cholangitis);

- odontogenic infections.

Contraindications:

- Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug;

- severe hypersensitivity reactions (eg, anaphylactic reactions) in an anamnesis to other beta-lactam antibiotics (cephalosporins, carbapenems or monobactams);

- Cholestatic jaundice and / or other liver function disorders caused by taking amoxicillin / clavulanic acid in a history;

- children under 2 years;

- Infectious mononucleosis;

- lymphocytic leukemia.

Carefully:

- Pseudomembranous colitis in the anamnesis, diseases of the digestive tract;

- liver failure;

- severe renal dysfunction;

- pregnancy and the period of breastfeeding;

- with simultaneous use with anticoagulants (see. section "Interaction with other drugs").

Pregnancy and lactation:

Studies in animals have not revealed data on the dangers of taking Amoxiclav^® Qtiktab during pregnancy and its effect on fetal embryonic development.

In one study in women with premature rupture of amniotic membranes, it was found that preventive therapy with amoxicillin / clavulanic acid may be associated with an increased risk of developing necrotizing enterocolitis in newborns. There is also information about the development in newborns of diarrhea and candidiasis of the mucous membranes of the oral cavity.

During pregnancy and during breast-feeding, the drug Amoxiclav^® Quiktab is used only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.

Amoxicillin and clavulanic acid penetrate into breast milk in small amounts, so taking the drug during breastfeeding should be continued only if there are clear indications.

Infants who are breastfed may develop sensitization, diarrhea, candidiasis of the oral mucosa. In such cases, breastfeeding should be discontinued.

Dosing and Administration:

Inside.

The dosage regimen is set individually depending on the age, body weight, function of the patient's kidneys and the severity of the infection. Tablets must be dissolved in half a glass of water (at least 30 ml) and mix thoroughly, then drink. Or hold the tablets in your mouth until completely dissolved, then swallow.

To reduce the risk of side effects from the gastrointestinal tract, you should take the drug at the beginning of the meal.

When using the drug in children under the age of 3 years, the tablets must be dissolved in water.

The duration of treatment is determined by the attending physician!

The duration of treatment depends on the severity of the infection and should not exceed 14 days without much need.

Adults and children 12 years of age or older or with a body weight of 40 kg or more the drug is prescribed at 500 mg / 125 mg 3 times a day.

For children aged 2 to 12 years The daily dose is usually 125 mg / 31.25 mg or 250 mg / 62.5 mg 3 times a day (depending on body weight, based on 20-40 mg of amoxicillin and 5-10 mg of clavulanic acid per kg of body weight). In severe, recurrent and chronic infections, these doses can be doubled (the maximum daily dose is 60 mg of amoxicillin and 15 mg of clavulanic acid per kg of body weight).

Patients with impaired renal function

In patients with creatinine clearance (CK) above 30 ml / min, there is no need for dose adjustment.

QC	Dosage regimen of Amoxiclav® Quicact in adults	Dosage regimen Amoxiclav® Quiktab in children
10-30 ml / min	500 mg / 125 mg twice a day (with an average and severe course of infection)	15 mg / kg 2 times a day (with an average and severe course of infection), not more than 500 mg / 125 mg 2 times a day
<10 ml / min	500 mg / 125 mg once a day (with an average and severe course of infection)	15 mg / kg once a day (with an average and severe course of infection), not more than 500 mg / 125 mg once a day
Hemodialysis	500 mg / 125 mg once a day and 500 mg / 125 mg during and after dialysis	15 mg / kg once a day and 15 mg / kg during and after dialysis

Patients with impaired hepatic function

When taking Amoxiclav^®Qwiktab should be careful. It is necessary to carry out regular monitoring of liver function. In the case of starting treatment with parenteral administration of the drug, therapy can continue to receive tablets Amoxiclav® Quicact.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their developmental frequency as follows: very often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Infectious and parasitic diseases

Often: Candidiasis of the skin and mucous membranes;

frequency unknown: growth of resistance of microorganisms.

Violations of the blood and lymphatic system

rarely: reversible leukopenia (including neutropenia), thrombocytopenia;

frequency is unknown: eosinophilia, thrombocytosis, reversible agranulocytosis, increased bleeding time and a reversible increase in prothrombin time, anemia (including reversible hemolytic anemia).

Immune system disorders

frequency unknown: angioedema, anaphylactic reactions, allergic vasculitis, a syndrome similar to serum sickness.

Disturbances from the nervous system

infrequently: dizziness, headache;

frequency is unknown: insomnia, agitation, anxiety, behavior change, reversible hyperactivity, aseptic meningitis, convulsions.

Disorders from the gastrointestinal tract

often: loss of appetite, nausea, vomiting, diarrhea;

Nausea is more often observed with ingestion of high doses. If violations of the GI tract are confirmed, they can be eliminated if you take the drug at the beginning of the meal.

infrequently: indigestion;

frequency unknown: antibiotic-associated colitis (including pseudomembranous and hemorrhagic colitis), black hairy tongue, gastritis, stomatitis.

In children, the discoloration of the surface layer of tooth enamel was very rare. Careful oral care helps prevent discoloration of tooth enamel, as it can often be eliminated with a toothbrush.

Disturbances from the skin and subcutaneous tissues

infrequently: skin rash, itching, hives;

rarely: multiforme exudative erythema;

frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Disorders from the kidneys and urinary tract

frequency unknown: crystalluria, interstitial nephritis, hematuria.

Disturbances from the liver and bile ducts

infrequently: increased activity of "hepatic" transaminases (moderate increase in alanine aminotransferase and / or aspartate aminotransferase is observed in patients receiving beta-lactam antibiotic therapy, however, its clinical significance is unknown);

frequency unknown: increased alkaline phosphatase activity, increased bilirubin concentration, hepatitis, cholestatic jaundice (noted with concomitant therapy with other penicillins and cephalosporins).

Undesirable liver side effects were observed mainly in men and elderly patients and may be associated with long-term therapy. These undesirable phenomena are very rare in children.

These signs and symptoms usually occur in the process or immediately after the end of therapy, but in some cases may not appear for several weeks after the completion of therapy. Undesirable phenomena, as a rule, are reversible. Undesirable phenomena from the liver can be severe, in extremely rare cases there have been reports of lethal outcomes. In almost all cases, these were patients with severe concomitant pathologies or patients who received potentially hepatotoxic drugs at the same time.

Overdose:

There are no reports of death or the occurrence of life-threatening side effects due to an overdose of Amoxiclav® Quicact.

Symptoms of overdose include gastrointestinal disorders (abdominal pain, diarrhea, vomiting) and water-electrolyte balance disorders. Reports of crystalluria caused by amoxicillin have been reported, which, in some cases, led to the development of renal failure. Possible development of seizures in patients with renal insufficiency or in patients receiving high doses of the drug.

In case of an overdose, the patient should be under the supervision of a physician, the treatment is symptomatic. Recommended gastric lavage and intake of adsorbents (Activated carbon).

Amoxicillin / clavulanic acid can be removed from the bloodstream by hemodialysis.

Interaction:

Antacids, glucosamine, laxative drugs, aminoglycosides slow absorption, ascorbic acid - increases the absorption of the drug.

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs and other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Simultaneous application with allopurinol can lead to the development of allergic reactions.

Simultaneous use of Amoxiclav® Quicact and methotrexate increases the toxicity of methotrexate.

The simultaneous use of disulfiram.

When combined with rifampicin there is a mutual weakening of the antibacterial effect.

Amoxiclav® Quicact should not be used concomitantly with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides because of a possible decrease in the effectiveness of Amoxiclav® Quicact.

It is not recommended to use together with probenecid. Probenecid reduces tubular secretion of amoxicillin. The simultaneous use of probenecid can lead to an increase and prolongation of the concentration of amoxicillin in the blood, but not clavulanic acid.

Simultaneous use of amoxicillin and digoxin can lead to an increase in the concentration of digoxin in the blood plasma.

Reduces the effectiveness of drugs, in the metabolism of which is formed p-aminobenzoic acid, ethinyl estradiol - risk of bleeding "breakthrough". With simultaneous application estrogen-containing oral contraceptives and amoxicillin should be used, if possible, other or additional methods of contraception.

Increases efficiency indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). In some cases, the drug may increase prothrombin time (PI) and international normalized ratio (INR) (with simultaneous application asenocoumarin or warfarin with amoxicillin), therefore caution should be exercised while using anticoagulants and Amoxiclav® Quicactum. If it is necessary to simultaneously use anticoagulants with PV or MNO should be closely monitored when the drug is prescribed or withdrawn, a correction of the dose of anticoagulants may be required.

In patients who received mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite of mycophenolic acid was observed - before taking the next dose of the drug by approximately 50%. Changes in this concentration can not accurately reflect the overall changes in the exposure of mycophenolic acid.

Special instructions:

Before starting treatment, it is necessary to interview the patient to identify in a history of hypersensitivity reactions to penicillins, cephalosporins or other β-lactam antibiotics.

In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics. In course treatment it is necessary to monitor the function of the organs of hematopoiesis, liver, kidneys.

Patients with severe renal dysfunction require adequate dose adjustment or an increase in the intervals between doses. section "Method of administration and dose"). It was stated that amoxicillin precipitates in urinary catheters, mainly after intravenous administration of large doses. It is necessary to regularly check the patency of catheters.

To reduce the risk of side effects from the GI tract, you should take the drug before or during meals.

When using high doses of Amoxiclav® Quiktab, patients with crystalluria should adequately compensate for fluid loss.

In the treatment of mild diarrhea (caused by Clostridium difficile) against the background of course treatment with Amoxiclav® Quiclab, antidiarrhoeal drugs that reduce intestinal motility should be avoided, kaolin- or attapulgite-containing antidiarrhoeal drugs may be used. With severe diarrhea, you should see a doctor.

Perhaps the development of superinfection due to the growth of insensitive microflora, which requires a corresponding change in antibacterial therapy.

If an antibiotic-associated colitis occurs, immediately discontinue Amoxiclav^® Quiktab, consult a doctor and begin appropriate treatment. Anti-peristaltic drugs in such situations are contraindicated.

In patients with impaired renal function or in patients receiving high doses of the drug, seizures may develop.

Treatment must continue for another 48-72 hours after the disappearance of clinical signs of the disease.

Amoxicillin and clavulanic acid can provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which can be the cause of a false positive reaction in the Coombs sample.

The use of amoxicillin and clavulanic acid is contraindicated in infectious mononucleosis, as it can provoke the appearance of a measles-like rash.

Lab tests, high concentrations of amoxicillin give a false positive reaction to urine glucose when using a Benedict reagent or Felling solution. It is recommended to use enzymatic glucose oxidase tests.

Cases of positive test results with the use of enzyme immunoassay were noted Bio-Rad Laboratories Platelia Aspergillus in patients receiving amoxicillin / clavulanic acid, who subsequently did not have an infection Aspergillus. Cross-reaction with polysaccharides was noted-Aspergillus and polyfurans with enzymatic immunoassay Bio-Rad Laboratories Platelia Aspergillus. Therefore, care should be taken when interpreting positive test results in patients receiving amoxicillin / clavulanic acid, and it must also be confirmed by other diagnostic methods.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions for the destruction of unused Amoxiclav^® Quicact.

Effect on the ability to drive transp. cf. and fur:

Data on the adverse effects of Amoxiclav^® Quiktab in recommended doses for the ability to drive a car or work with mechanisms there. However, due to the possibility of developing side effects from the central nervous system, such as dizziness, headache, convulsions, during treatment, care should be taken when driving and engaging in other activities that require concentration and speed of psychomotor reactions.When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:

Tablets are dispersible, 125 mg + 31.25 mg, 250 mg + 62.50 mg.

Packaging:

2 tablets per blister from Al / Al.

By 5, 7 or 10 blisters together with instructions for medical use in a pack of cardboard.

Storage conditions:

In the original packaging in a place protected from moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004109

Date of registration:30.01.2017

Expiration Date:30.01.2022

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp22.02.2017

Illustrated instructions

Instructions

Amoxiclav® Quicactab (Amoksiklav® Quicktabs)